It has been shown that alkylphosphocholine analogs are preferentially taken up and retained by solid tumor cancer cells, as compared to normal cells, such as fibroblasts. Accordingly, the use of alkylphoshocholine analogs in methods for imaging and treating cancerous solid tumors has previously been disclosed.
In U.S. Patent Publication No. 2014/0030187, which is incorporated by reference herein in its entirety, Weichert et al. disclose using analogs of the base compound 18-(p-iodophenyl)octadecyl phosphcholine (CLR1404; see FIG. 1) for detecting and locating, as well as for treating, solid tumor cancers. For example, if the iodo moiety is an imaging-optimized radionucleide, such as iodine-124 ([124I]-CLR1404), the analog can be used in positron emission tomography-computed tomography (PET/CT) or single-photon emission computed tomography (SPECT) imaging of solid tumors, or in other imaging/detection applications. Alternatively, if the iodo moiety is a radionuclide optimized for delivering therapeutic doses of radiation to the solid tumors cells in which the analog is taken up, such as iodine-125 or iodine-131 ([125I]-CLR1404 or [131]-CLR1404), the analog can be used to treat the solid tumors.
In U.S. Patent Publication No. 2010/0284929, which is incorporated by reference herein in its entirety, Pinchuk et al. extend this idea to the visual detection of solid tumors. Specifically, Pinchuk et al. disclose further analogs of CLR1404, wherein the iodo moiety is substituted with a fluorophore. For example, if the iodo moiety is substituted with a boron-dipyrromethene (BODIPY) core (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene), the resulting compound (CLR1501; see FIG. 2) is taken up by solid tumor cells, which can then be visually detected/imaged. CLR1404 analogs having other fluorphores substituted for the iodo moiety, such as IR-775 (CLR1502; see FIG. 3), can similarly be used to visually identify/detect solid tumors or cells from non-solid tumors.
Multiple myeloma (MM) is a type of cancer that occurs in circulating blood cells (i.e., plasma B cells), rather than in solid tissue. Multiple myeloma is a universally fatal disease, comprising 15% of hematological malignancies and 1% of all cancers. It has a median survival of 5-7 years from diagnosis. While newer drugs, such as bortezomib and lenalidomide, have exhibited increased response to therapy, patients inevitably relapse and become resistant to therapy.
Multiple myeloma tumor cells have been shown to be highly radiosensitive; however, there are currently no mechanisms of targeted delivery of radiation to the tumor cells. Therefore, radiotherapy with either radiation or radiolabeled compounds is not currently utilized for the clinical treatment of multiple myeloma.
Accordingly, there is a need for new and effective methods of targeting therapies, particularly radiotherapies, to multiple myeloma tumor cells, and for new methods of detecting/imaging multiple myeloma tumor cells within a patient.